tbuckley/cabot-search huggingface dataset:
Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses
Authors: Felix Bayerl, Philippa Meiser, Sainitin Donakonda, Anna Hirschberger, Sebastian B. Lacher, Anna-Marie Pedde, Chris D. Hermann, Anais Elewaut, Moritz Knolle, Lukas Ramsauer, Thomas J. Rudolph, Simon Grassmann, Rupert Öllinger, Nicole Kirchhammer, Marcel Trefny, Martina Anton, Dirk Wohlleber, Bastian Höchst, Anne Zaremba, Achim Krüger, Roland Rad, Anna C. Obenauf, Dirk Schadendorf, Alfred Zippelius, Veit R. Buchholz, Barbara U. Schraml, Jan P. Böttcher
Journal: Immunity (2023)

Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective anti-cancer immunity is thought to require cDC1s to sustain T cell responses within tumors, but it is poorly understood how this function is regulated and whether its subversion contributes to immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE2) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability to locally orchestrate anti-cancer CD8+ T cell responses. Mechanistically, cAMP signaling downstream of the PGE2-receptors EP2 and EP4 was responsible for the programming of cDC1 dysfunction, which depended on the loss of the transcription factor IRF8. Blockade of the PGE2-EP2/EP4-cDC1 axis prevented cDC1 dysfunction in tumors, locally reinvigorated anti-cancer CD8+ T cell responses, and achieved cancer immune control. In human cDC1s, PGE2-induced dysfunction is conserved and associated with poor cancer patient prognosis. Our findings reveal a cDC1-dependent intratumoral checkpoint for anti-cancer immunity that is targeted by PGE2 for immune evasion.
Thymoma
Authors: Chad D. Strange, Jitesh Ahuja, Christina Thornton, Erik Vakil, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Despite being the most common epithelial tumor in the anterior mediastinum, thymomas are uncommon tumors, as mediastinal pathology is unusual in general. There is controversy in terms of classification, staging, and clinical outcomes. Most publications about thymomas comprise small series of cases in which the authors have proposed their own views about classification, staging, or clinical behavior. In more recent times, some issues around thymomas have been resolved, but nevertheless, it is important to highlight that the published literature is rather empiric at best with little detail and with a wide spectrum of disparity in terms of pathology. It is important to clarify that thymoma is not the benign counterpart of thymic carcinoma nor is thymic carcinoma the malignant form of thymoma. Both conditions, thymoma and thymic carcinoma, represent unique clinicopathological entities, which require proper delineation not only for diagnostic purposes but also for prognosis, treatment, and outcomes. The clinical outcome in patients with thymoma is closely linked to the pathological stage at the time of diagnosis. In tumors that are encapsulated or minimally invasive, it is possible that only surgical resection offers a good clinical outcome while in those patients with invasive disease other treatment options such as radiation therapy and/or chemotherapy become possible alternatives.
Mediastinal Germ Cell Tumors
Authors: Chad D. Strange, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Primary mediastinal germ cell tumors represent a unique group of tumors that share similar histopathological features with their counterparts in the gonads. The histogenesis of mediastinal germ cell tumors is not completely understood. Because the histology and in some cases the clinical features of these tumors may also be similar to those in the gonads, it is highly important to properly evaluate the imaging in those patients. Nevertheless, these tumors represent a diagnostic challenge and often a mediastinal biopsy may be the one used to start medical treatment in these patients. Therefore, it is highly important to become familiar not only with the different histopathological growth patterns of these tumors but also with their immunohistochemical characteristics. In general, mediastinal germ cell tumors follow similar immunophenotypes as those in the gonads. However, it is important to highlight that clinically, the majority of patients with mediastinal germ cell tumors are young men and these tumors appear to affect this particular population.
Thymic Carcinoma
Authors: Chad D. Strange, Jitesh Ahuja, Christina Thornton, Erik Vakil, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Thymic carcinoma reflects a heterogeneous group of tumors that may be grouped into low- and high-grade tumors. Currently, thymic carcinoma is well recognized in the literature as a distinct histopathological category, but in the past, it was often conflated with the so-called malignant thymoma. Authoritative publications such the Atlas of Tumor Pathology from the Armed Forces Institute of Pathology did not have a designation for the thymic carcinoma in their earlier versions. It is highly important to note that the diagnosis depends upon good radiological–pathological correlation and the absence of carcinoma elsewhere in the presence of an anterior mediastinal mass. The most common thymic carcinoma is squamous cell in origin. Others include thymic adenocarcinoma, NUT carcinoma, and salivary gland-type carcinomas of the thymus. Staging is done with the TNM system. Immunohistochemical markers have considerable overlap among the entities constituting thymic carcinoma.
Pneumoconiosis
Authors: Sujith V. Cherian, Anupam Kumar, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

The International Labor Organization defines pneumoconiosis as the accumulation of dust in the lungs and the tissue reactions to its presence. The diagnosis of any pneumoconiosis involves a detailed evaluation of exposure to any agent known to cause interstitial lung diseases (ILD). Given the long latency of several of these diseases, a complete occupational history and exclusion of other causes of ILD are required. Within this context along with consistent radiographic and pulmonary function abnormalities, a diagnosis of pneumoconiosis can be made with reasonable certainty. Asbestos is a general term for a heterogeneous group of hydrated magnesium silicate that tends to break up into fibers. These fibers, when inhaled into the lungs, can cause a spectrum of lung disorders including benign conditions such as pulmonary fibrosis and malignant conditions such as lung cancer and mesothelioma. Asbestosis is the interstitial pneumonitis and fibrosis caused by inhalation of asbestos fibers. Silicosis represents varying degrees of lung disease caused by inhalational exposure to crystalline silica (silicon dioxide), usually in the form of quartz (present in granite and sandstone). Other forms of crystalline silica include cristobalite and tridymite. Over time, exposure to inhaled silica can cause worsening inflammation and some patients may develop pulmonary fibrosis. Hard metal is different from heavy metal (e.g., lead, chromium, cadmium, mercury) and is produced by compacting powdered tungsten carbide with cobalt (between 3–25%) in a process called sintering which is then heated to approximately 1500 °C rendering it very hard and thus making it suitable for sharpening metals, drills, and polishing hard metal parts to precise dimensions, including diamonds and dental prostheses. Moreover, it is used in varying amounts to make coolants, which when aerosolized is easily inhaled—thus causing downstream effects within the airways and lungs.
Mediastinal Lymphoproliferative Disorders
Authors: Sergio Pina-Oviedo, Chad D. Strange
Journal: Thorax (2023)

This chapter discusses the clinical, radiologic, histopathologic, and relevant cytogenetic and molecular alterations of reactive and malignant mediastinal lymphoproliferative disorders. All these entities comprise a significant proportion of cases seen by clinicians, radiologists, and pathologists, particularly those specialized in thoracic or hematologic diseases. Clinically, these lesions manifest as mediastinal lymphadenopathy or a mediastinal mass with or without disease elsewhere, and the clinical and radiologic suspicion is usually that of malignancy. A biopsy (fine needle aspiration, core biopsy, video-assisted thoracoscopy, mediastinoscopy, or excisional biopsy) is required to establish a diagnosis and the modality of this procedure depends on the location of a lesion within the mediastinum. Benign or reactive conditions discussed here include sarcoidosis, other granulomatous lymphadenitis with a known etiology, Castleman disease, IgG4-related disease/sclerosing mediastinitis, and the histiocytic disorders Langerhans cell histiocytosis and Rosai-Dorfman disease. For some of these lesions, morphology and a limited panel of ancillary studies are sufficient to establish a diagnosis. However, for some others clinico-radiologic and laboratory correlation (cultures, PCR, serology) are required to render a complete diagnostic interpretation. Malignant mediastinal hematolymphoid disorders discussed here include common and rare neoplasms at this location such as classic Hodgkin lymphoma, non-Hodgkin lymphomas (T-lymphoblastic leukemia/lymphoma, diffuse large B-cell lymphoma, primary mediastinal [thymic] large B-cell lymphoma, mediastinal gray zone lymphoma, T-cell lymphomas), myeloid sarcoma, and follicular dendritic cell (FDC) sarcoma. In contrast to reactive conditions, each of these malignant disorders has a particular clinic-radiologic presentation and tends to present with chest pain, dyspnea, cough, effusions, and superior vena cava syndrome if there is bulky disease. Along with proper morphologic evaluation, the diagnosis of these neoplasms requires the use of ≥1 ancillary studies to arrive at the correct diagnosis, and nowadays most cases require cytogenetics, fluorescence in situ hybridization, and/or molecular analyses to identify potential prognostic or predictive markers.
Interstitial Lung Diseases
Authors: Rodeo Abrencillo, Isabel C. Mira-Avendano, Rosa M. Estrada-Y-Martin, Irina Sadovnikov, Colin Zuchowski, Gokhan Kuyumcu, Anjali Taneja, Gabriel Duhancioglu, Usha Jayagurunathan, Matthew LeComte, Diana Palacio, Michelle Hershman, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Interstitial lung diseases (ILDs) comprise a heterogeneous group of complex chronic lung diseases. Patients with ILD present with progressive dyspnea, cough, and impaired pulmonary function resulting in quality of life issues. Mortality in patients with ILD can be as high as in some types of cancer. Patients with idiopathic pulmonary fibrosis (IPF), the most common of the idiopathic ILDs, have a median life expectancy of only 3–5 years from the time of diagnosis. Various ILD subtypes show overlap in pathophysiology and imaging appearance, which can confound ILD classification. Many experts conditionally agree that the reference standard for diagnostic decision-making and diagnosis of ILDs is through a multidisciplinary discussion including pulmonologist, radiologist, and pathologist. Multidisciplinary discussion of suspected IPF cases results in better interobserver agreement, better congruence, and higher confidence in the final diagnoses, and in certain cases, changes the impression to a non-IPF diagnosis. Multidisciplinary discussion also aids in making a decision to pursue invasive diagnostic procedures such as transbronchial biopsy, bronchoalveolar lavage, and surgical lung biopsy, especially when the risks of such procedures are high because of disease severity, advanced age, and comorbidities.
Non-Small Cell Carcinoma
Authors: Donald R. Lazarus, Chad D. Strange, Jitesh Ahuja, Girish S. Shroff, Bradley S. Sabloff, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Lung cancer is the leading cause of cancer death in the world, with over two million new cases and over 1.7 million deaths reported in 2018. In the United States alone lung cancer is responsible for more deaths than colon, breast, and prostate cancer combined. Most patients with lung cancer present with advanced disease, and prognosis is poor. Non-small cell lung carcinomas (NSCLC) account for approximately 80% of primary lung cancers. Tobacco use is responsible for 85–90% of cases of lung cancer in countries where smoking is common. Cough is the most common symptom present in patients with lung cancer, occurring in 45–75% of patients. Other common presenting symptoms include weight loss, dyspnea, hemoptysis, and chest pain. NSCLC is staged using the tumor-node-metastasis (TNM) classification system as developed by the International Association for the Study of Lung Cancer, which has undergone periodic revisions based on metadata. The use of immunohistochemical studies and molecular analysis plays an important role in the diagnosis and treatment alternatives.
Benign and Malignant Mesenchymal Tumors of the Lung
Authors: David I. Suster, Craig Mackinnon, Jitesh Ahuja, Chad D. Strange, Mathieu Marcoux, Patricia M. de Groot, Mylene T. Truong
Journal: Thorax (2023)

Mesenchymal tumors of the lung are rare neoplasms that may range from benign, incidental lesions to highly aggressive sarcomas. Given that the lung is the most common site of spread for soft tissue sarcomas, pulmonary mesenchymal tumors are most often the result of metastatic spread from primary lesions at other sites rather than representing primary tumors arising from the lung parenchyma. However, primary lung mesenchymal neoplasms do occur and include nearly all histogenetic categories. This includes tumors of various different subtypes including fibroblastic, smooth muscle, adipocytic, neurologic, vascular, bone, cartilage, and undifferentiated tumors. Malignant mesenchymal tumors are more common in the lung than benign ones and often present with an aggressive clinical course. Both the benign and malignant lesions that occur as lung primaries share similar histologic, immunohistochemical, and molecular genetic profiles as compared to their soft tissue counterparts. The diagnosis of these tumors usually requires clinical, pathologic, and radiologic correlation and will often necessitate the use of ancillary studies to secure the diagnosis.
Miscellaneous Conditions
Authors: Chad D. Strange, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

In this chapter of miscellaneous conditions in the mediastinum, we have included several conditions that are not related in any way with each other. These conditions even though may be infrequent, they may pose significant problems in the diagnosis, mainly when the only available material is a small biopsy. In some of these lesions such as fibrosing mediastinitis, the final interpretation may require more clinical data while in other such as ependymoma; the diagnosis requires a good clinical and radiological correlation. In addition, we have included in this chapter multilocular thymic cyst, a benign cystic tumor that requires final interpretation only after the entire mediastinal cyst has been surgical resected. Essentially, all these conditions depicted in this chapter represent problematic lesions when confronted with a small biopsy. Needless to say, the role that diagnostic imaging plays is highly important in asserting that the lesion is located in the mediastinal region.
Neuroendocrine Neoplasms of the Lung
Authors: Philip G. Ong, Chad D. Strange, Jitesh Ahuja, Girish S. Shroff, Bradley S. Sabloff, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Neuroendocrine tumors (NETs) represent a heterogeneous group of neoplasms with a morphologic spectrum that ranges from well-differentiated tumors such as typical carcinoids of the lung, intermediate-grade neoplasms like atypical carcinoids, and high-grade or poorly differentiated tumors such as small cell lung carcinoma and large-cell neuroendocrine carcinoma. These tumors comprise 25% of primary lung neoplasms and are thought to arise from specialized neuroendocrine cells that form a part of the epithelial lining of the bronchial tree. These cells, known as pulmonary neuroendocrine cells (PNECs) or Kulchitshy cells, are phylogenetically ancient and believed to be of endodermal origin. They are also found in the gastrointestinal tract. The management and prognosis of pulmonary neuroendocrine tumors vary widely. In this chapter, we will discuss the clinical, radiological, and pathological correlates of the spectrum of neuroendocrine neoplasms of the lung to provide information that can be directly applied to clinical practice.
The Pleura
Authors: Chad D. Strange, Jitesh Ahuja, Saadia A. Faiz, Horiana B. Grosu, William C. Harding, Keerthana Keshava, Carlos A. Jimenez, Vickie R. Shannon, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Pleural abnormalities are often a manifestation of intrathoracic and systemic diseases caused by an extensive list of neoplastic and nonneoplastic conditions. Both neoplastic and nonneoplastic pleural diseases can present with similar clinical features. Nonneoplastic disorders of the pleura may result from a variety of infectious as well as drug- and trauma-related causes. Primary pleural disease owing to a myriad of inflammatory and neoplastic pleural disorders is less common, but nonetheless relevant due to its potential to cause devastating respiratory compromise. Moreover, many of the benign tumors of the pleura closely mimic malignant disease in their radiographic and histologic appearance. In this chapter, we will discuss the clinical, radiographic, and pathologic correlates of the spectrum of primary and secondary diseases of the pleura. The intent of this multidisciplinary approach is to provide a detailed overview and update of diseases of the pleura that can be directly applied to clinical practice and to stimulate basic research investigations in areas where there are unanswered questions.
Airspace Diseases and Pulmonary Nodules
Authors: Rodeo Abrencillo, Isabel C. Mira-Avendano, Rosa M. Estrada-Y-Martin, Diana Palacio, Anjali Taneja, Gabriel Duhancioglu, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Diseases that present as lung nodules and airspace opacities include cryptogenic organizing pneumonia, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, lipoid pneumonia, and sarcoidosis. The most important diagnostic decision in cryptogenic organizing pneumonia is the exclusion of any other potential causes. The secondary causes of organizing pneumonia include infectious processes, exposures to chemical or fumes, antibiotics, connective tissue diseases, radiation, and chemotherapy including new checkpoint inhibitors. The eosinophilic disorders comprise rare infiltrative parenchymal lung diseases characterized by the presence of eosinophils in the interstitium and alveolar space with conservation of the lung architecture. Allergic bronchopulmonary aspergillosis occurs in patients with prior bronchial disease. Following exposure to Aspergillus, bronchial disease–associated mucus plugs produce a complex chronic immune and inflammatory reaction inside the bronchi and in the lung parenchyma with secondary damage and impairment of the normal mucociliary clearance. Lipoid pneumonia is also known as cholesterol pneumonia, paraffinoma, or golden pneumonia. This unusual type of pneumonia can be seen predominantly in bedridden patients; however, it can occur in any age group. The cause of lipoid pneumonia may be either endogenous or exogenous. Endogenous causes may include gastroesophageal reflux, while exogenous causes may include aspiration of substances such as mineral or vegetable oil, petroleum jelly, or in some cases radiographic contrast media. Pulmonary sarcoidosis is a multisystemic granulomatous syndrome of unknown origin, which affects the lungs in 90% of cases, although any organ can be compromised during the course of the disease. It also has a varied clinic presentation, from asymptomatic incidentally found to progressive life-threating involvement of the affected organ, such as lung fibrosis.
Tumors of Uncertain Histogenesis
Authors: Chad D. Strange, Jitesh Ahuja, Girish S. Shroff, Bradley S. Sabloff, Pushan P. Jani, Alexis Preston, Sarah A. Holevinski, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

This is a variable group of tumors for which a specific cell of origin is debatable. The tumors in this group do not share any histopathological characteristics. In general, this group of tumors occur rarely and their malignant potential is difficult to determine in a small biopsy. In some cases, the primary tumors are considered benign but may spread into lymph nodes. These tumors an occur in the periphery of the lung or in central location. Even though a small biopsy is obtained as a diagnostic procedure in the assessment of these tumors, more often than not, the final interpretation is only after complete surgical resection has been accomplished and after extensive immunohistochemical analysis has been performed. Diagnostic imaging is important in establishing whether the tumor is a solitary tumor mass; however, it is difficult to separate these tumors by those means, ultimately relying on surgical resection for definitive diagnosis. Immunohistochemical studies are important in the assessment of these tumors.
Emphysema and Cystic Lung Disease
Authors: Selvin Jacob, Mark T. Warner
Journal: Thorax (2023)

Emphysema is a form of chronic obstructive pulmonary disease (COPD), that is defined by the Global Initiative for chronic obstructive lung disease (GOLD). It is a disease that affects the air spaces distal to the terminal bronchiole, and further characterized by abnormal permanent dilation of the air spaces. This leads to destruction of these air spaces and lung parenchyma with loss of elasticity. Cystic lung disease has a broad differential diagnosis, which includes Alpha 1-Antitrypsin deficiency, Birt-Hogg-Dube syndrome, and Lymphoid interstitial pneumonia, to name a few. Pathophysiological development of these various diseases varies from airway obstruction to remodeling of the lung, which leads to cystic development. An accurate diagnosis can be challenging, and management is dependent on the disease. A combination of imaging, serum tests, genetic tests, and clinical features can aid in differentiating between various etiologies. A biopsy is often required for definitive diagnosis. This chapter presents an overview of Emphysema, as well as various Cystic Lung Diseases.